You are on page 1of 5

Kaohsiung Journal of Medical Sciences (2016) 32, 191e195

Available online at www.sciencedirect.com

ScienceDirect
journal homepage: http://www.kjms-online.com

ORIGINAL ARTICLE

Outcomes and prognostic factors of simple partial


cystectomy for localized bladder urothelial cell
carcinoma
I-Hung Shao a, Ying-Hsu Chang b,c,*, Kai-Jie Yu b,c, Po-Hung Lin b,c,
Chung-Yi Liu b,c, Cheng-Keng Chuang b,c, See-Tong Pang b,c
a

Division of Urology, Department of Surgery, Lotung Pohai Hospital, Yilan, Taiwan


Division of Urology, Department of Surgery, Chang Gung Memorial Hospital at Linkou,
Chang Gung University College of Medicine, Taoyuan, Taiwan
c
Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung
University, Taoyuan, Taiwan
b

Received 30 September 2015; accepted 7 December 2015

Available online 27 March 2016

KEYWORDS
Bladder tumor;
Partial cystectomy;
Urothelial carcinoma

Abstract Radical cystectomy has remained the gold standard for recurrent superficial or
muscle invasive bladder tumor. However, partial cystectomy still has a role in those who reject
or have contraindications for radical cystectomy. In this study, we sought to identify predictors
of bladder recurrence and overall survival after simple partial cystectomy. We included 27 patients with bladder tumor who received simple partial cystectomy without pelvic lymph node
dissection between March 2000 and September 2013. Adjuvant chemotherapy or radiation
therapy was prescribed according to the pathological results. Parameters were compared on
the basis of bladder recurrence and overall survival. During a mean follow-up time of
39 months, five patients (18.5%) experienced bladder recurrence. An older age, a higher pathological stage, positive surgical margins, and distant metastases were significant predictors of
overall survival (p Z 0.031, p Z 0.001, p Z 0.001, and p Z 0.011, respectively). Meanwhile,
previous bladder instillation and positive surgical margins were significant predictors of
bladder recurrence (p Z 0.026 and p Z 0.027, respectively). The rate of consecutive distant
metastases (33.3%) was almost twice the rate of bladder recurrence (18.5%), and six patients
developed consecutive distant metastases without first experiencing bladder recurrence. In
patients who received a simple partial cystectomy as an alternative treatment, previous
bladder instillation and positive surgical margins were significant predictors of bladder recurrence. Patients with an older age, positive surgical margins, and consecutive distant metastases had worse overall survival. Partial cystectomy with routine lymph node dissection may be a
better option for achieving favorable long-term outcomes.

Conflicts of interest: All authors declare no conflicts of interest.


* Corresponding author. Division of Urology, Department of Surgery, Chang Gung Memorial Hospital, 5 Fu-Shing Street, Kweishan, Taoyuan
333, Taiwan.
E-mail address: changyinghsu@gmail.com (Y.-H. Chang).
http://dx.doi.org/10.1016/j.kjms.2016.02.008
1607-551X/Copyright 2016, Kaohsiung Medical University. Published by Elsevier Taiwan LLC. This is an open access article under the
CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

192

I.-H. Shao et al.


Copyright 2016, Kaohsiung Medical University. Published by Elsevier Taiwan LLC. This is an
open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/
by-nc-nd/4.0/).

Introduction
Urothelial carcinoma of the urinary bladder is strongly
associated with environmental factors and age. The incidence and prevalence rates increase with age, peaking in
the 8th decade of life [1,2]. In the United States in 2007,
bladder urothelial carcinoma accounted for 7% of all cancers [1]. In addition to its high prevalence, bladder cancer
is fatal, accounting for 3% of all cancer deaths in the United
States in 2007. However, due to advancements in treatment
strategies and modalities, bladder cancer mortality
decreased by 5% between 1990 and 2004, despite a
continuous rise in the incidence of the disease [1].
Radical cystectomy is one of the main treatment options
for localized muscle invasive bladder urothelial carcinoma
and select nonmuscle invasive disease. However, along with
cancer control, radical cystectomy also results in some
degree of reduction in the quality of life; it impacts
continence, body image, and potency. These consequences
make bladder preservation during treatment an important
goal, for both patients and surgeons, in advanced bladder
cancer cases.
A partial cystectomy with pelvic lymph node dissection
can be reserved for select patients with a solitary lesion for
whom radical cystectomy is otherwise contraindicated and
a sufficient margin can be obtained. Some previous studies
noted the comparable prognosis of radical cystectomy and
partial cystectomy with adequate patient selection [3,4].
In this study, we analyzed patients who underwent
simple partial cystectomy without pelvic lymph node
dissection with the aim of identifying predictors of bladder
cancer recurrence and overall survival in this population.

Materials and methods


Twenty-seven patients who underwent a simple partial
cystectomy without pelvic lymph node dissection at our
hospital between March 2000 and September 2013 were
included in this study. These patients were diagnosed with
bladder urothelial carcinoma, and the diagnosis was
confirmed by transurethral resection of bladder tumors
(TUR-BT). All patients met the criteria for radical cystectomy, but underwent simple partial cystectomy due to
medical considerations or on the basis of their own decision. Computed tomography scans and bone scans were
performed for staging before the operation. The absence of
lymph node and distant metastases was determined by
imaging studies. All bladder lesions were solitary with
adequate resection margins of at least 1 cm. No neoadjuvant chemotherapy or radiation therapy was administered. Adjuvant chemotherapy or radiation therapy was
prescribed according to the pathological results, i.e., if at
least one of the following criteria was met: pathological
Stage T3 or Stage T4 disease, or positive surgical margins.

The prognosis analysis was based on overall survival and


recurrence-free survival. Parameters included general patient characteristics (sex, age, body mass index), tumor
factors (pathological T stage, tumor histology, tumor size,
and pathological grade), surgical factors (American Society
of Anesthesiologists score and surgical margins), and previous bladder tumor conditions (previous intravesical
instillation including chemotherapy or bacillus CalmetteGuerin (BCG) instillation and previous TUR-BT history and
number). Here, the TUR-BT history did not refer to TUR-BT
for the same bladder tumor, but to any previous superficial
bladder tumor history for which bladder preservation
therapy with TUR-BT was performed.
Statistical analyses were performed using SPSS version
17 software (Linkou, Taoyuan, Taiwan). Statistical methods
included frequency descriptions and a Kaplan-Meier survival analysis. The study was approved by the Institutional
Review Board.

Results
Patient characteristics are listed in Table 1. The mean age
of patients who underwent partial cystectomy was
70.6 years (range 49e90 years). The mean follow-up time
after partial cystectomy was 39.0 months. The patients
were predominantly male, with a male to female ratio of
5.8.
Overall, 63% (17) of patients had pathological Stage T1
or Stage T2 disease, while Stage T3 and Stage T4 disease
accounted for 33.3% (9) and 3.7% (1) of cases, respectively.
The most common tumor histology was infiltrating carcinoma (74%); other histologies included papillary (14.8%),
sarcomatoid (7.4%), and poorly differentiated types (3.7%).
In terms of pathological grade, high-grade tumors accounted for 88.9% of all cases.
Fourteen (51.9%) patients had superficial bladder tumors
for which they had previously received TUR-BT. Among
these 14 patients, 11 (40.7%) had undergone TUR-BT once
and three had received TUR-BT at least twice. Previous
intravesical therapies including epirubicin, mitomycin, and
BCG instillation were prescribed according to individual
status in keeping with the National Comprehensive Cancer
Network guidelines [5]. Pathological specimen examination
showed that four (14.8%) patients had residual cancer at
the surgical margin and 23 (85.2%) patients had clear surgical margins.
During a mean follow up of 39.0  39.0 months, five
(18.5%) patients experienced tumor recurrence in the
bladder, nine (33.3%) patients developed distant metastasis
postsurgically, and 10 (37%) patients died. Results of the
univariate analysis performed using KaplaneMeier survival
curves for overall survival are shown in Table 2. Significant
predictors of overall survival in patients who received
partial cystectomy were: age > 70 years, a higher

Partial cystectomy for localized bladder tumor


Table 1

Patient characteristics.

Mean patient age (y)


70.6  10.7
Mean follow-up time (mo)
39.0  39
24.4  2.88
Body mass index (kg/m2)
Sex
Male
23 (85.2)
Female
4 (14.8)
Pathological T stage
1
10 (37.0)
2
7 (25.9)
3
9 (33.3)
4
1 (3.7)
Mean tumor size (cm)
2.97  1.7
Pathological pattern
Infiltrating
20 (74)
Papillary
4 (14.8)
Sarcomatoid
2 (7.4)
Poorly differentiated
1 (3.7)
Pathological grade
High
24 (88.9)
Low
3 (11.1)
ASA score
1
1 (3.7)
2
13 (48.1)
3
13 (48.1)
Previous TUR-BT
No
13 (48.1)
Yes
14 (51.9)
Previous number of TUR-BTs
0
13 (48.1)
1
11 (40.7)
2
1 (3.7)
3
1 (3.7)
4
1 (3.7)
Previous intravesical instillation
Epirubicin
2 (7.4)
Mitomycin
1 (3.7)
BCG
1 (3.7)
Surgical margin
Negative
23 (85.2)
Positive
4 (14.8)
Bladder recurrence
No
22 (81.5)
Yes
5 (18.5)
Distant metastasis
No
18 (66.7)
Yes
9 (33.3)

(49e90)
(3.13e148.4)
(20.7e34.4)

Data are presented as mean  SD (range) or n (%).


ASA score Z American Society of Anesthesiologists score;
BCG Z bacillus CalmetteeGuerin; SD Z standard deviation;
TUR-BT Z transurethral resection of bladder tumors.

pathological T stage, positive surgical margins, and


consecutive distant metastases (p Z 0.031, p Z 0.001,
p Z 0.001, and p Z 0.011, respectively).
Results of the univariate analysis of recurrent-free survival are shown in Table 3. Previous bladder intravesical
instillation and positive surgical margins were significant
predictors of bladder tumor recurrence (p Z 0.026 and

193
Table 2
survival.

Univariate analysis of predictors of overall


No. of cases Mean survival No. of
time (mo) deaths

Sex
Female
4
Male
23
Age (y)*
< 70
13
 70
14
Body mass index (kg/m2)
 24
12
> 24
13
Pathological T stage*
1
10
2
7
3
9
4
1
Tumor size (cm)
<2
6
 2 and < 4
12
4
9
Histology
Papillary
4
Infiltrating
20
Others
3
(sarcomatoid and
poorly
differentiated)
Pathological grade
Low
3
High
24
ASA score
1
1
2
13
3
13
Previous TUR-BT
No
13
Yes
14
Number of
previous TUR-BTs
0
13
1
11
2
3
Previous intravesical instillation
No
24
Yes
3
Surgical margin*
Negative
23
Positive
4
Bladder recurrence
No
22
Yes
5
Distant metastasis*
No
18
Yes
9

27.8  10
88.0  16

2
8

0.121

118.7  18
47.2  13

2
8

0.031*

4
4

0.670

94.8  11
26.0  7
91.1  25
4.6

2
4
3
1

0.001*

57.8  10
65.6  15
81.9  23

1
5
4

0.870

63.8  12
93.5  18
82.0  15

3
6
1

0.539

88.3  20
75.3  16

1
9

0.312

0
4
6

0.202

103.2  18
33.2  5.4
67.2  15
82.4  20

5
5

0.875

67.2  15
89.4  20
16.1  15

5
4
1

0.440

10
0

0.582

93.0  16
16.5  8

7
3

0.001*

92.4  16
44.9  23

7
3

0.154

102.2  18
37.9  14

4
6

0.011*

94.7  19.9
57.1  12.3

*p < 0.05.
ASA score Z American Society of Anesthesiologists score; TURBT Z transurethral resection of bladder tumors.

194

I.-H. Shao et al.

Table 3 Univariate analysis of predictors of bladder


recurrence-free survival.
No. of cases

Sex
Female
4
Male
23
Age (y)
< 70
13
 70
14
Body mass index (kg/m2)
 24
12
> 24
13
Pathological T stage
1
10
2
7
3
9
4
1
Tumor size (cm)
<2
6
 2 and < 4
12
 4 cm
9
Histology
Papillary
4
Infiltrating
20
Others
3
(sarcomatoid
and poorly
differentiated)
Pathological grade
Low
3
High
24
ASA score
1
1
2
13
3
13
Previous TUR-BT
No
13
Yes
14
No. of previous TUR-BTs
0
13
1
11
2
3
Previous
intravesical
instillation*
No
24
Yes
3
Surgical margin*
Negative
23
Positive
4

Mean
No. of
recurrence-free deaths
time (mo)

0
5

0.346

126.2
87.7

2
3

0.606

124.4
69.4

2
3

0.637

90.6
34.96
114.1

2
1
2
0

0.956

57.8
93.6
116.3

1
2
2

0.956

68.3
118.7

1
4
0

0.539

0
5

0.393

0
3
2

0.774

95.1
116.5

2
3

0.700

95.1
135.2
8.4

2
1
2

0.078

129.7
8.1

10
0

0.026*

129.5
5.3

3
2

0.027*

*p < 0.05.
ASA score Z American Society of Anesthesiologists score; TURBT Z transurethral resection of bladder tumors.

p Z 0.027, respectively). Patients with a history of more


than two previous TUR-BTs appeared more likely to have
tumor recurrence, although this was not statistically significant (p Z 0.078).

Discussion
Ninety percent of urinary bladder cancers are urothelial
cell carcinomas [6], with muscle invasive disease accounting for 80% of urothelial tumors at initial presentation.
Radical cystectomy remains the most frequently utilized
surgical intervention for clinical Stage T2 and Stage T3
bladder urothelial carcinoma without lymph node or distant
metastases. Cystectomy may also be indicated for select
superficial bladder tumors, for example, recurrent pT1
high-grade tumors.
For patients in whom radical cystectomy is indicated,
but who wish to preserve the urinary bladder, alternative
treatments include radical TUR-BT, partial cystectomy, and
neoadjuvant concomitant chemoradiotherapy. Partial cystectomy plays a role in select patients with appropriately
located solitary tumors and resectable margins. A standard
partial cystectomy should include bilateral pelvic lymph
node dissection to confirm lymph node stage.
Previous studies have reported on prognosis with standard
partial cystectomy, along with predictors of survival or
recurrence. Holzbeierlein and colleagues [3] reviewed the
cases of 58 select patients who underwent partial cystectomy
with pelvic lymph node dissection for bladder urothelial carcinoma and were followed up for 33 months. They reported
that partial cystectomy with pelvic lymph node dissection can
result in comparable outcomes in specifically selected patients. In addition, concomitant carcinoma in situ and lymph
node metastasis were found to be predictors of advanced
recurrence. Smaldone and colleagues [4] reviewed the cases
of 25 patients with primary solitary T2 or high-grade T1 tumors
who received preoperative radiation for 5 days and a single
dose of intraoperative intravesical chemotherapy followed by
partial cystectomy with pelvic lymph node dissection. Over a
follow-up period of 11 years, the cancer-specific 5-year survival was 84%. To the best of our knowledge, the role and
prognosis of simple partial cystectomy have not been discussed in previous studies.
In this study, we aimed to identify prognostic predictors
for patients who underwent a simple partial cystectomy.
During a mean follow-up time of 39 months, the bladder
tumor recurrence rate was 18.5%, with an overall survival
rate of 63%. The significant predictors of poor overall survival were: age > 70 years, a higher T stage, positive surgical margins, and consecutive distant metastases. These
predictors were similar to the prognostic factors of patients
who underwent a radical cystectomy [7e9]. In addition,
previous intravesical bladder instillation and positive surgical margins were significant predictors of bladder tumor
recurrence. This can be explained by the fact that patients
for whom intravesical instillation was indicated had a T1
high-grade tumor, coexisting carcinoma in situ, or a
recurrent bladder tumor. These patients are at high risk for
bladder tumor recurrence after partial cystectomy. Patients with positive surgical margins after a partial cystectomy also had a high probability of bladder tumor
recurrence despite adjuvant chemotherapy or radiation
therapy. Thus, a more aggressive follow up is important in
these patients. Although not significant, patients with a
history of multiple previous TUR-BTs (>2) were more likely
to have bladder tumor recurrence (p Z 0.078).

Partial cystectomy for localized bladder tumor


In our study, we determined that the incidence rate of
consecutive distant metastases (33.3%) was almost twice
that of recurrence in the bladder (18.5%). This rate was also
higher than that reported for another case series of partial
cystectomy with pelvic lymph node dissection [3]. Among
patients with distant metastases, six developed consecutive distant metastases without first having a recurrence in
the bladder. This may be due to the high potential for
lymph node metastasis, even though preoperative
computed tomography scans were negative for lymph node
metastasis. In patients with potential lymph node metastases, the bilateral pelvic lymph nodes played an important
role, not only in the staging diagnosis, but also in terms of
the survival benefit, because consecutive distant metastases had a significant effect on overall survival.

Conclusion
For patients who underwent simple partial cystectomy as
an alternative treatment, previous bladder instillation (due
to previous high-grade or carcinoma in situ tumors) and
positive surgical margins were significant predictors of
bladder tumor recurrence. Patients aged > 70 years, and
those with positive surgical margins and consecutive distant
metastases, had worse overall survival.
With adequate patient selection and proper postoperative follow up, simple partial cystectomy without
pelvic lymph node dissection could provide a favorable
prognosis for local bladder tumor recurrence. However, the
lymph node or distant metastasis rate appeared relatively
higher in our patients than in patients who received partial
cystectomy with pelvic lymph node dissection in other reported case series. A possible reason for the variation in
results may be that potential lymph node metastases were
missed on preoperative images. For patients who are eligible

195
for partial cystectomy, simultaneous lymph node dissection
may result in more favorable long-term outcomes in terms of
overall survival or distant metastases, even in those without
suspected lymph node metastasis.

References
[1] Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, et al. Cancer
statistics, 2008. CA Cancer J Clin 2008;58:71e96.
[2] Parkin DM. The global burden of urinary bladder cancer. Scand
J Urol Nephrol Suppl 2008;218:12e20.
[3] Holzbeierlein JM, Lopez-Corona E, Bochner BH, Herr HW,
Donat SM, Russo P, et al. Partial cystectomy: a contemporary
review of the Memorial Sloan-Kettering Cancer Center experience and recommendations for patient selection. J Urol 2004;
172:878e81.
[4] Smaldone MC, Jacobs BL, Smaldone AM, Hrebinko Jr RL. Longterm results of selective partial cystectomy for invasive urothelial bladder carcinoma. Urology 2008;72:613e6.
[5] Clark PE, Agarwal N, Biagioli MC, Eisenberger MA,
Greenberg RE, Herr HW, et al. Bladder cancer. J Natl Compr
Canc Netw 2013;11:446e75.
[6] Lopez-Beltran A. Bladder cancer: clinical and pathological
profile. Scand J Urol Nephrol Suppl 2008;218:95e109.
[7] Konety BR, Dhawan V, Allareddy V, Joslyn SA. Impact of hospital and surgeon volume on in-hospital mortality from radical
cystectomy: data from the health care utilization project. J
Urol 2005;173:1695e700.
[8] Nielsen ME, Shariat SF, Karakiewicz PI, Lotan Y, Rogers CG,
Amiel GE, et al. Advanced age is associated with poorer bladder
cancer-specific survival in patients treated with radical cystectomy. Eur Urol 2007;51:699e706.
[9] Bagrodia A, Grover S, Srivastava A, Gupta A, Bolenz C,
Sagalowsky AI, et al. Impact of body mass index on clinical and
cost outcomes after radical cystectomy. BJU Int 2009;104:
326e30.